Targeting neuronal FTL1 rescues cognitive impairments in aging
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ABSTRACT:
PROVIDER: PRJNA1047170 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:TARGETING NEURONAL FTL1 RESCUES COGNITIVE IMPAIRMENTS IN AGING
| PRJNA1049409 | ENA
Project description:Understanding cellular and molecular drivers of age-related cognitive decline is necessary to identify targets to restore cognition at old age. Here we report that ferritin light chain 1 (FTL1) is a pro-aging neuronal factor that impairs cognition. Targeting neuronal FTL1 in the hippocampi of aged mice elicits synaptic and metabolic-related molecular changes and rescues cognitive impairments. Our data identify neuronal FTL1 as a key molecular mediator of cognitive rejuvenation.
2025-07-08 | GSE249105 | GEO
Project description:Understanding cellular and molecular drivers of age-related cognitive decline is necessary to identify targets to restore cognition at old age. Here we report that ferritin light chain 1 (FTL1) is a pro-aging neuronal factor that impairs cognition. Targeting neuronal FTL1 in the hippocampi of aged mice elicits synaptic and metabolic-related molecular changes and rescues cognitive impairments. Our data identify neuronal FTL1 as a key molecular mediator of cognitive rejuvenation.
2024-12-01 | GSE249504 | GEO
Project description:<p>Background: Chronic use of antipsychotic drugs is associated with neuronal damage and cognitive impairment, potentially mediated by alterations in gut microbiota metabolites, although the specific metabolite involved remains unknown.</p><p>Objective: To identify the key metabolite responsible for antipsychotic-induced synaptic and cognitive impairment and assess the potential for its reversal through targeted supplementation.</p><p>Design: Mice were chronically treated (8 weeks) with olanzapine, risperidone, or clozapine. In the olanzapine model, gut microbiota (16S rRNA and shotgun metagenomic sequencing) and metabolites (untargeted metabolomics) were analyzed, identifying ergothioneine depletion, validated in olanzapine-treated patients. Causality was tested via fecal microbiota transplantation (FMT) and ergothioneine supplementation. Neuronal-specific PTP1B knockout mice elucidated mechanistic pathways.</p><p>Results: Chronic olanzapine treatment caused gut microbial dysbiosis, disrupted intestinal barrier integrity, and impaired cognitive function in mice. A key finding was the depletion of ergothioneine, the gut microbiota-derived metabolite, in both the blood and brain of mice, and in the blood of patients receiving olanzapine. This depletion was associated with a loss of ergothioneine-producing Cyanobacteria and subordinate taxa. Similar ergothioneine depletion and cognitive impairments were observed in risperidone- and clozapine-treated mice. Ergothioneine supplementation or FMT effectively prevented olanzapine-induced cognitive and synaptic impairments. Mechanistically, ergothioneine attenuated olanzapine-induced hippocampal oxidative stress and inhibited the redox-sensitive phosphatase PTP1B. Furthermore, neuronal- or hippocampal neuronal-specific deletion of PTP1B abolished olanzapine-induced synaptic and cognitive impairments. </p><p>Conclusions: The significant reduction of ergothioneine induced by antipsychotic treatment leads to cognitive impairment, highlighting gut microbiota-derived metabolites as potential therapeutic targets for improving cognitive function in patients undergoing antipsychotic therapy.</p>
2026-04-08 | MTBLS12751 | MetaboLights
Project description:Endogenous compensatory changes influence trajectory of brain aging, cognitive decline and Alzheimer’s Disease (AD) risk, however, the identities of underlying mechanisms have remained elusive. A screen for hippocampal dentate granule cell (DGC) synapse loss-induced factors identified a secreted phospholipase, Pla2g2f, whose expression increases in DGCs during aging. Pla2g2f deletion in DGCs exacerbates aging-associated synapse loss, emergence of inflammatory microglia, reactive astrogliosis, lipid dysregulation and memory impairment. Boosting Pla2g2f in DGCs during aging prevents these pathophysiological impairments and modifies trajectory of cognitive decline. In human microglia-neuron coculture experiments PLA2G2F mediates intercellular signaling to decrease lipid burden. Boosting Pla2g2f expression in an aging-sensitive AD model reduces amyloid load and preserves memory. Thus, PLA2G2F functions as a compensatory neuroprotective factor that counteracts aging-associated cognitive decline.
2026-08-10 | GSE261906 | GEO
Project description:Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline [snRNA-seq]
| PRJNA1269311 | ENA
Project description:Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline [scRNA-seq]
| PRJNA1269306 | ENA
Project description:Changes in peripheral CD8+ T cells are a prominent hallmark of immune aging. While infiltrating CD8+ T cells are implicated in aging and neurodegenerative disease-related pathology in the brain, the role of aged non-infiltrating CD8+ T cells has yet to be fully defined. Here, we show that targeting activated aged peripheral CD8+ T cells rescues age-related cognitive decline. Using heterochronic parabiosis and single cell transcriptomics analysis we observed that aged peripheral CD8+ T cells maintain properties intrinsic to their age, being refractory to the effects of a young or aged systemic milieu. Systemic exposure of young mice to aged CD8+ T cells elicited synaptic-related aging transcriptional signatures in the hippocampus and impaired cognition. Inhibiting migration of aged peripheral CD8+ T cells to lymph nodes mitigated pro-aging effects on the young hippocampus. Conversely, targeting aged CD8+ T cells restored synaptic-related signatures in the aged hippocampus and ameliorated cognitive impairments. Mechanistically, we identified granzyme k (GZMK) as a secreted age-associated CD8+ T cell-derived factor that impairs cognitive function. Together, our data identify activated aged CD8+ T cells and their secreted factors as potential therapeutic targets to rescue cognition in old age.
2026-06-25 | GSE266454 | GEO
Project description:Changes in peripheral CD8+ T cells are a prominent hallmark of immune aging. While infiltrating CD8+ T cells are implicated in aging and neurodegenerative disease-related pathology in the brain, the role of aged non-infiltrating CD8+ T cells has yet to be fully defined. Here, we show that targeting activated aged peripheral CD8+ T cells rescues age-related cognitive decline. Using heterochronic parabiosis and single cell transcriptomics analysis we observed that aged peripheral CD8+ T cells maintain properties intrinsic to their age, being refractory to the effects of a young or aged systemic milieu. Systemic exposure of young mice to aged CD8+ T cells elicited synaptic-related aging transcriptional signatures in the hippocampus and impaired cognition. Inhibiting migration of aged peripheral CD8+ T cells to lymph nodes mitigated pro-aging effects on the young hippocampus. Conversely, targeting aged CD8+ T cells restored synaptic-related signatures in the aged hippocampus and ameliorated cognitive impairments. Mechanistically, we identified granzyme k (GZMK) as a secreted age-associated CD8+ T cell-derived factor that impairs cognitive function. Together, our data identify activated aged CD8+ T cells and their secreted factors as potential therapeutic targets to rescue cognition in old age.
2025-05-02 | GSE266467 | GEO
Project description:Changes in peripheral CD8+ T cells are a prominent hallmark of immune aging. While infiltrating CD8+ T cells are implicated in aging and neurodegenerative disease-related pathology in the brain, the role of aged non-infiltrating CD8+ T cells has yet to be fully defined. Here, we show that targeting activated aged peripheral CD8+ T cells rescues age-related cognitive decline. Using heterochronic parabiosis and single cell transcriptomics analysis we observed that aged peripheral CD8+ T cells maintain properties intrinsic to their age, being refractory to the effects of a young or aged systemic milieu. Systemic exposure of young mice to aged CD8+ T cells elicited synaptic-related aging transcriptional signatures in the hippocampus and impaired cognition. Inhibiting migration of aged peripheral CD8+ T cells to lymph nodes mitigated pro-aging effects on the young hippocampus. Conversely, targeting aged CD8+ T cells restored synaptic-related signatures in the aged hippocampus and ameliorated cognitive impairments. Mechanistically, we identified granzyme k (GZMK) as a secreted age-associated CD8+ T cell-derived factor that impairs cognitive function. Together, our data identify activated aged CD8+ T cells and their secreted factors as potential therapeutic targets to rescue cognition in old age.
2025-05-02 | GSE266468 | GEO